Kynurenine Pathway Pathologies: Do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)

Editor's Comment: The kynurenine pathway is a metabolic pathway leading to the production of nicotinamide adenine dinucleotide (NAD+), which is derived from the essential amino acid tryptophan. Disruptions of this pathway have been implicated in several inflammatory neurological diseases, including Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Parkinson's disease, cancer, depression and schizophrenia. In this article, Adele Blankfield proposes that the "upregulation of the tryptophan kynurenine pathway offers an explanatory model for an immunological connection between malnutrition and infection, and for the pathophysiological and neurological complications of severe trauma and illness, CFS/FM included."

Kynurenine Pathway Pathologies: Do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)

By Adele Blankfield

Abstract

The definition of dual tryptophan pathways has increased the understanding of the mind-body, body-mind dichotomy. The serotonergic pathway highlights the primary (endogenous) psychiatric disorders. The up-regulation of the kynurenine pathway by physical illnesses can cause neuropathic and immunological disorders associated with secondary neuropsychiatric symptoms.

Tryptophan and nicotinamide deficiencies fall within the protein energy malnutrition (PEM) spectrum. They can arise if the kynurenine pathway is stressed by primary or secondary inflammatory conditions and the consequent imbalance of available catabolic/anabolic substrates may adversely influence convalescent phase efficiency.

The replacement of depleted or reduced NAD+ levels and other cofactors can perhaps improve the clinical management of these disorders.

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) appear to meet the criteria of a tryptophan-kynurenine pathway disorder with potential neuroimmunological sequelae. Aspects of some of the putative precipitating factors have been previously outlined.

An analysis of the areas of metabolic dysfunction will focus on future directions for research and management.